AzTrials
AzTrials

Malignant AscitesPhase 2NCT01200121

Bevacizumab as a Palliative Treatment for Patients With Symptomatic Malignant Ascites Due to Advanced-stage Gastrointestinal Cancers

A Phase 2 study testing Bevacizumab in people with Malignant Ascites and Gastrointestinal Cancers, run by AIO-Studien-gGmbH at 26 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Malignant ascites represents a severe clinical problem for physicians and patients being confronted with this common symptom of advanced-stage gastrointestinal cancer. Unfortunately, there is no standardized and evidence-based treatment for malignant ascites and therapies which are commonly being used are only… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Ascites, Gastrointestinal Cancers
What is being tested?
Bevacizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
53 participants
Where
26 sitesGermany
Study dates
Feb 2010to Dec 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years
  • Written informed consent has been obtained prior to inclu¬sion into the study
  • Patient is capable and willing to comply with the study
  • Histologically confirmed esophageal, gastric, pancreatic, cholangiocellular, hepatocellular, or colorectal carcinoma
  • Cytologically confirmed ascites OR diagnosis of an exsudate (total protein in ascites > 30 g/l) clinically suggestive for malignant ascites OR morphological diagnosis of peritoneal carcinosis by CT , MRT or ultrasound
  • Ascites clinically judged as not responsive to conventional systemic therapies for primary malignancy
Show all 23Show fewer
  • Ascites clinically judged as not responsive to diuretics
  • At the time of inclusion paracentesis required at least twice within past 4 weeks.
  • Before inclusion of the patient into the study, a 4-week screening period will allow for a stringent evaluation of the patient regarding fulfillment of inclusion and exclusion criteria. Importantly, no treatments for malignant ascites other than paracentesis and diuretics are allowed during the 4-week screening period.
  • ECOG performance score 0-3
  • Life expectancy > 12 weeks
  • Laboratory parameters:
  • Hematology
  • Neutrophils > 1,500/µl
  • Platelets > 100,000/µl
  • Hemoglobin >= 9 g/dl or 5.59 mmol/l Hemastasiology
  • INR <= 1.5 x ULN and aPTT <= 1.5 x ULN within past 7 dClinical chemistry
  • Creatinine clearance > 30 ml/min, serum creatinine < 2.5 x ULN
  • Serum bilirubin < 3.0 x ULN
  • Alkaline phosphatase and transaminases < 3.0 x ULN (in case of liver metastases < 7 x ULN)
  • Urinalysis:
  • Patients with < 2+ proteinuria on dipstick urinalysis.
  • Patients with >= 2+ proteinuria on dipstick urinalysis, who demonstrate < 2.0 g of protein/24 h on 24-h urine collection

Who cannot join

  • Concomitant malignancies other than gastrointestinal cancers (Patients with curatively treated basal and squamous cell carcino¬ma of the skin and / or in-situ carci¬noma of the cervix are eli¬gible).
  • Bacterial peritonitis as indicated by laboratory results (neutrophil count > 250 / µl ascites) or clinical suspicion
  • Hemorrhagic ascites (ascites hematocrit > 2%)
  • Transudative ascites (total protein in ascites < 30 g/l)
  • Parallel treatment with anti-tumor agents other than the study medication from inclusion into the study until safety follow-up. Chemotherapy may be continued if started before screening phase (- 4 weeks before inclusion). Parallel Treatment with Bevacizumab i.v. is not allowed.
  • Therapy naïve patients
Show all 32Show fewer
  • Parallel treatment of ascites with measures other than para¬centesis, diuretics, and the study drugs from 4 weeks before inclusion into the study until safety follow-up.
  • Patients with extensive metastases of the liver making up > 70% of the total liver mass
  • Child C cirrhosis of the liver
  • Occlusion or thrombosis of the portal vein.
  • Evidence of current and symptomatic central nervous system (CNS) metas¬ta¬ses or spinal cord compression.
  • Clinically significant cardiovascular diseases, e.g., un¬con¬trolled hypertension, uncontrolled arrhythmia, hemoptoe, cardiovascular accident within the last 6 months before treatment start, unstable angina, congestive heart failure (CHF) NYHA grade III/IV, symptomatic coronary heart disease, peripheral arterial disease stage >= II.
  • History of fistula formation involving an internal organ (e.g. tracheo-oesophagal, bronchopleural, biliary, vagina and bladder)
  • Major surgical procedure, open biopsy, or significant trau¬matic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
  • Concomitant treatment with intravenous Bevacizumab for primary malignancy from inclusion into study until safety follow-up. Prior treatment with Bevacizumab for primary malignancy is not exclusionary.
  • Serious non-healing wound, ulcer or bone fracture.
  • Radiotherapy for purposes other than local control of symp¬toms.
  • Evidence of bleeding diathesis or coagulopathy.
  • Hematopoietic diseases.
  • Known intra-abdominal inflammatory process or serious gastrointestinal ulceration.
  • History of chronic intestinal diseases associated with severe diarrhea.
  • Thrombo-embolic events or severe hemorrhage (<= 6 months before treatment start).
  • Known hypersensitivity to the test drug Bevacizumab
  • Evidence of any other disease, metabolic dysfunction, physi¬cal examination finding, or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related compli¬cations.
  • With the only exception of full dose (INR > 1.5) oral coumarin-derived anticoagulants, the use of full dose anticoagulants is allowed as long as the INR or a PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for at least two weeks at the time of randomisation.
  • Patients who participated within the last 30 days prior to enrolment in a clinical trial and received a non approved investigational drug (e.g. follow up within the trial is not exclusionary).
  • Patients who have participated in this study before.
  • Women, lactating, pregnant or of childbearing potential and fertile men not using a highly effective contraceptive method . [Women of childbearing potential must have a negative pregnancy test (serum ß HCG) within 7 days before the first dose of study drug].
  • Patients who are committed to an institution by virtue of an order issued either by the judicial or the administra¬tive authorities (according to § 40 (1) 4 AMG).
  • Patients who are underage or patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 (4) and § 41 (2) and (3) AMG).
  • Patients with a history of a psychological illness or con¬di¬tion such as to interfere with the patient's ability to un¬der¬stand the requirements of the study.
  • Patients who possibly are dependent on the sponsor or investigator.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

Germany26 sites

  • Vivantes Klinikum Am Urban, Klinik für Innere Medizin

    Berlin, State of Berlin, 10967

  • VIVANTES Klinikum Neukölln, Onkologisches Zentrum Vivantes Süd

    Berlin, State of Berlin, 12351

  • Charité (Campus Virchow-Klinikum), Med. Klinik mit Schwerpunkt Hämatologie und Onkologie

    Berlin, State of Berlin, 13353

  • Vivantes Klinikum Spandau, Klinik für Innere Medizin

    Berlin, State of Berlin, 13585

  • Medizinisches Versorgungszentrum, Onkologischer Schwerpunkt

    Berlin-Zehlendorf, State of Berlin, 14195

  • Klinikum Deggendorf, Medizinische Klinik II

    Deggendorf, Bavaria, 94469

  • Kliniken Essen-Mitte, Klinik f. intern. Onkologie u. Hämatologie

    Essen, North Rhine-Westphalia, 45136

  • Universitätsklinikum Essen, Klinik für Innere Medizin - Tumorforschung

    Essen, North Rhine-Westphalia, 45147

  • Klinikum der J.W. Goethe-Univerisität Frankfurt, Klinik für Allgemein- und Viszeralchirurgie

    Frankfurt am Main, Hesse, 60590

  • Universitätslinikum der Martin-Luther Universität Halle-Wittenberg, Klinik für Innere Medizin IV

    Halle, Saxony-Anhalt, 06120

  • Universitätsklinikum Hamburg - Eppendorf, Onkologisches Zentrum

    Hamburg, Free and Hanseatic City of Hamburg, 20246

  • MVZ für Innere Medizin in Hamburg-Eppendorf

    Hamburg, Free and Hanseatic City of Hamburg, 20249

  • Klinikum Region Hannover GmbH, Krankenhaus Siloah, Med. Klinik III (Hämatologie & Onkologie)

    Hanover, Lower Saxony, 30449

  • Onkologische Schwerpunktpraxis Hildesheim, Im Medicinum

    Hildesheim, Lower Saxony, 31135

  • Universitätsklinikum Leipzig, Klinik für Gastroenterologie und Rheumatologie

    Leipzig, Saxony, 04103

  • Klinikum Leverkusen gGmbH, Medizinische Klinik III

    Leverkusen, North Rhine-Westphalia, 51375

  • Klinikum Ludwigsburg, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie

    Ludwigsburg, Baden-Wurttemberg, 71640

  • Johannes Gutenberg Universität, Universitätsklinikum, I. Medizinische Klinik und Poliklinik

    Mainz, Rhineland-Palatinate, 55131

  • Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus, Hämatologie/Onkologie/Gastroonkologie

    Mönchengladbach, North Rhine-Westphalia, 41063

  • Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie/Nephrologie

    Neumünster, Schleswig-Holstein, 24534

  • Internistische Praxis und Tagesklinik

    Neustadt (Sachsen), Saxony, 01844

  • Ernst von Bergmann Klinikum, Zentrum für Hämatologie/Onkologie/Strahlenheilkunde

    Potsdam, Brandenburg, 14467

  • Prosper-Hospital, Medizinische Klinik I

    Recklinghausen, North Rhine-Westphalia, 45659

  • Onkologische Schwerpunktpraxis

    Wendlingen, Baden-Wurttemberg, 73240

  • Klinikum Wetzlar-Braunfels, Medizinische Klinik II

    Wetzlar, Hesse, 35578

  • Hämatologisch Onkologische Praxis Würselen

    Würselen, North Rhine-Westphalia, 52146

Other trials in Germany

About this study

Official title: Double-blind, Placebo-controlled, Randomized Phase II-study Investigating the Efficacy of Bevacizumab for Symptom Control in Patients With Malignant Ascites Due to Advanced-stage Gastrointestinal Cancers

Malignant ascites represents a severe clinical problem for physicians and patients being confronted with this common symptom of advanced-stage gastrointestinal cancer. Unfortunately, there is no standardized and evidence-based treatment for malignant ascites and therapies which are commonly being used are only temporarily effective. Newer modes of therapy, such as the application of the tri-functional antibody catumaxomab, are associated with significant side effects and are limited to patients in stages of good overall performance. Therefore, there is still an urgent need for more effective, longer-lasting, and less toxic modes of treatment for peritoneal effusions caused by gastrointestinal cancers.

Preclinical data strongly suggest that bevacizumab might be a very effective agent for the treatment of malignant ascites, which is in large part caused by the hyperpermeability-promoting factor VEGF. Emerging clinical results from cancer patients with malignant ascites treated with bevacizumab add further support to this idea. Bevacizumab has been tested in a variety of large clinical trials, has a good toxicity profile, and is effective in a number of human cancers underlying malignant ascites.

In the present study, Bevacizumab will be administered as an intraperitoneal infusion at an absolute standardized dosage of 400 mg. This dosage was chosen because it is comparable to the approved standard dosage for intravenous administration which was also used in both studies reporting the successful and safe intraperitoneal administration of Bevacizumab to patients with malignant ascites. Finally, a standardized dosage seems more practical in the particular patient population treated in this study.

Being tested
Bevacizumab, Placebo
Keywords
Symptomatic malignant ascites due to advanced-stage gastrointestinal cancers
Medical subject headings
Gastrointestinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabDrug

    Also called Avastin

    Patients will receive paracentesis as needed for symptom con¬trol. In addition, patients will receive up to 4 intraperitoneal administrations of 400 mg Bevacizumabafter paracentesis has been performed. During the 8-week treatment period, a minimum interval of 14 days will be kept between applications of the study medication.

  • PlaceboOther

    Patients will receive paracentesis as needed for symptom con¬trol. In addition, patients will receive up to 4 intraperitoneal administrations of Placebo after paracentesis has been performed. During the 8-week treatment period, a minimum interval of 14 days will be kept between applications of the study medication.

Study groups in NCT01200121
Study groupRoleWhat they receive
Arm A BevacizumabExperimental48 patients randomized into arm A will receive repeated intra¬peritoneal application of Bevacizumab
Receives: Drug: Bevacizumab
Arm B PlaceboPlacebo comparator26 patients randomized into arm B will receive repeated intra¬peritoneal application of Placebo
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. paracentesis-free survival (ParFS)

    The first primary endpoint will consist of paracentesis-free survival (ParFS) which will be calculated as the time period between the initial puncture after randomization to the first subsequent paracentesis or other symptomatic treatments for ascites with the exception of diuretics or until death (whichever occurs first)

    Measured: one year

Secondary outcomes (9)

  1. Best Response (BR)

    Best Response representing the longest period of time from one paracentesis until next paracentesis within the treatment period or, if longer, from the last paracentesis performed within the treatment period until first subsequent symptomatic treatment for ascites with the exception of diuretics (before end of the standard 4 week follow-up) or, if longer, from the last paracentesis performed within the treatment period until death (before end of the standard 4 week follow-up) or, if longer, from the last paracentesis performed within the treatment period until 4 week follow-up

    Measured: 12 weeks from 1st application

  2. Volume of ascites

    Volume of ascites drained by routine paracentesis (ascites volume minus lavage volumes, if applicable)

    Measured: 12 weeks

  3. Quality of life

    Quality of life as assessed by standardized questionnaires

    Measured: 12 weeks

  4. Changes in ECOG performance status

    Calculation: 12 weeks minus baseline

    Measured: baseline and 12 weeks

  5. Pharmacokinetics of Bevacizumab and VEGF concentrations

    Measured: 12 weeks

  6. Proportions of patients with adverse events grades 3, 4, or 5.

    Measured: 12 weeks

  7. Proportions of patients with adverse events of special interest

    any grade of gastrointestinal perforation, gastrointestinal fistulas or other internal fistulas, wound-healing disturbances, hemorrhagic events and arterial thrombo-embolic events.

    Measured: 12 weeks

  8. All adverse events

    Measured: 12 weeks

  9. Changes in laboratory values and vital signs.

    Calculation: Value from later timepoints minus baseline value

    Measured: baseline, every two weeks up to week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionAug 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01200121
Sponsor's protocol ID
AIO-SUP-0108
Status last verified
Apr 2015
First submitted
9 Sep 2010
Last updated
13 Apr 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab in people with Malignant Ascites and Gastrointestinal Cancers, run by AIO-Studien-gGmbH at 26 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

paracentesis-free survival (ParFS) (time frame: one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01200121.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in